The efficacy of tricyclic antidepressants (TCAs) has been decisively established for endogenous depressive disorders. Monoamine oxidase inhibitors (MAOI's) are shown to be useful for patients with depressive, neurotic and phobic symptoms, although it has never been demonstrated that MAOI's are superior to TCA's for any patient group. It is our contention that there exist subtypes of depressive disorder, some of whom respond preferentially to MAOI's. These differences have been obscured by the use of diagnostically mixed patient samples in previous studies of TCA vs. MAOI efficacy. We therefore propose to conduct a study with a diagnostically homogeneous group of depressed patients manifesting symptoms of atypical depressive disorder, including reactivity of mood, weight gain, increased sleeping and reversed diurnal variation with mood worse in the evening. We expect these patients to respond better to MAOI's than TCA's. If this is the case, we will have identified an effective treatment for a sizeable group of depressed patients for whom no standard treatment program is now available. The study is designed to investigate whether patients diagnosed as atypical depressives will respond specifically to MAOI's (phenelzine) and not TCA's (imipramine). Following a 10-day single blind placebo period, patients will be randomized to a double-blind six-week study contrasting phenelzine, imipramine and placebo. In order to gain a further understanding of biochemical processes mediating drug response, we will investigate the relationship of percent platelet MAO inhibition to outcome of treatment with phenelzine. Plasma levels of imipramine and desipramine will be determined during the course of the study.